Diseases, such as inflammatory bowel disease, manifest in various regions of the intestinal tract, such as regions of the small intestine. There exist pharmaceutically active binding polypeptides which are effective in the treatment of inflammatory bowel disease when administered systemically. For example, anti-TNF-alpha antibodies have demonstrated efficacy in treating inflammatory bowel diseases. However, because these antibodies are commonly delivered by injection (i.e. intravenous, subcutaneous or intramuscular) and neutralise TNF-alpha systemically, their use may be associated with serious side effects, including reactivation of tuberculosis and a long-term risk of malignancy. Moreover, the parenteral route of administration and the large doses required make these antibody therapies expensive and hardly accessible for patients.
Oral administration of such polypeptides for local effect in a target region of the intestinal tract would be preferable, due to for example reduced cost and the convenience of this dosage form. In addition, oral administration may provide reduced immunogenicity as compared to parenteral administration forms and may reduce or eliminate unnecessary systemic exposure to the polypeptide.
To achieve this goal, a suitable release profile must be achieved. That is, the activity of the polypeptide must be maintained after transit through the upper intestinal tract including the stomach and suitably the duodenum and the desired dosage of active polypeptide must be delivered to the desired location of the intestinal tract.
Pharmaceutical compositions of the present invention may, in at least some embodiments, have one or more of the following advantages compared to those of the prior art:                (i) a sustained release profile,        (ii) a delayed release profile,        (iii) targeted release to one or more regions of the intestinal tract,        (iv) substantially consistent release to all regions of the intestinal tract from the duodenum to the anal canal (i.e. avoiding ‘dose dumping’),        (v) reduced host immune response to the delivered polypeptide compared to parenteral administration,        (vi) reduced systemic exposure to pharmaceutically active agent,        (vii) reduced dosage required for therapeutic effects,        (viii) reduced cost of production,        (ix) maintained or improved thermal stability of polypeptide.        